TMPA 是一种具有高亲和力的Nur77拮抗剂,与Nur77结合导致LKB1在细胞质中释放和穿梭,以激活AMPKα。TMPA 能有效地降低血糖,减轻 II 型 db/db、高脂饮食和链脲霉素诱导的糖尿病小鼠的胰岛素抵抗。TMPA 能减少人类 T 细胞的 RICD,也可用于癌症和 T 细胞凋亡失调的研究。
生物活性 | TMPA is a high-affinityNur77antagonist that binds toNur77leading to the release and shuttling ofLKB1in the cytoplasm to activateAMPKα. TMPA effectively lowers blood glucose and attenuatesinsulinresistance in type II db/db, high-fat diet and streptozotocin-induced diabetic mice. TMPA reduces RICD (restimulation-induced cell death) in human T cells, can also be used in studies ofcancerand T-cellapoptosisdysregulation[1][2]. |
体外研究 (In Vitro) | TMPA (5, 10, 20, 40, 80 μM; 6 h or 10 μM; 0.5, 1, 3, 6, 12, 24, 36, 48 h) antagonizes the Nur77-LKB1 interaction in a dose- and time-dependent manner in hepatic LO2 cells[1]. TMPA (10 μM; 6 h) enhances the LKB1-AMPKα interaction but decreases the LKB1-Nur77 interaction under physio logical conditions in Lo2 cells[1]. TMPA binds directly to LBD in specific conformation[1]. TMPA (10, 20 μM; 6 h) induces LKB1 nuclear export to activate AMPKα in Lo2 cells[1]. TMPA (10, 50, 100 μM; 4 h) impairs human T-cell RICD (restimulation-induced cell death)[2].
Cell Viability Assay[2] Cell Line: | T cells | Concentration: | 10, 50, 100 μM | Incubation Time: | 4 h | Result: | Significantly reduced T-cell RICD in a dose-dependent manner. |
Western Blot Analysis[1] Cell Line: | Hepatic LO2 cells | Concentration: | 10, 20 μM | Incubation Time: | 6 h | Result: | Led to an increase of LKB1 phosphorylation at Ser428. |
Western Blot Analysis[1] Cell Line: | Hepatic LO2 cells | Concentration: | 5, 10, 20, 40, 80 μM | Incubation Time: | 6 h | Result: | Increased the amount of phosphorylation of AmPKα in a dose- and time-dependent manner. Rescued the LKB1-AmPKα interaction by reducing the nur77-lKb1 interaction when at 10 μM. |
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体内研究 (In Vivo) | TMPA (50 mg/kg; i.p.; single daily for 19 days) is capable of lowering blood glucose and improving glucose tolerance in type II diabetic mice[1].
Animal Model: | Male C57BL/KsJ-Leprdb/Leprdb(db/db) mice (10-week-old; type II diabetic model)[1]. | Dosage: | 50 mg/kg | Administration: | Intraperitoneal injection; single daily for 19 days. | Result: | Significantly reduced blood glucose at day 7 and persisted during the remainder of the test. Increased the amount of phosphorylated AMPKα in the liver of mice. |
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : ≥ 100 mg/mL(262.83 mM) *"≥" means soluble, but saturation unknown. 配制储备液 1 mM | 2.6283 mL | 13.1413 mL | 26.2826 mL | 5 mM | 0.5257 mL | 2.6283 mL | 5.2565 mL | 10 mM | 0.2628 mL | 1.3141 mL | 2.6283 mL |
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以下溶剂前显示的百 分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (6.57 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.57 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (6.57 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.57 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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